SUMMARY The prevalence of obesity in children has increased dramatically in recent years. However, conventional treatment has had poor long-term effectiveness. The short-term goal of this competitive renewal application is to provide protected time for the Principal Investigator, David Ludwig, MD, PhD, for an additional 5 years of mentoring and patient-oriented research. During the first period of support, Dr. Ludwig had primary responsibility for the training of 10 full-time graduate students, post-doctoral fellows and junior faculty. In addition, he supervised 14 other individuals for research rotations or career development. A total of 34 scientific articles (including 17 original research studies) were published during the first 4 years of the award period, with additional articles submitted or in preparation. Two new R01 grants were obtained during the initial award period that, together with other ongoing or available studies, provide outstanding opportunities for training junior investigators. The long-term mentoring goal of this project is to help train clinical scientists in the areas of pediatric obesity and nutrition by providing opportunities at all levels (undergraduate, medical student, resident, fellow and junior faculty) to work on state-of-the-art clinical research. The long-term scientific goals are to explore the effects of specific dietary factors on body weight regulation and risk for type 2 diabetes and heart disease, and use these findings to design more effective approaches to obesity treatment and chronic disease prevention. The specific dietary factors of interest include macronutrient composition, glycemic index, fiber, dairy, beverage consumption, food processing and prenatal diet. Toward this end, we will employ controlled feeding study (Specific Aim #1), behaviorally-oriented outpatient clinical trials (Specific Aim #2) and prospective observational analyses (Specific Aim #3). The research environment is ideal to support these goals, including the presence of the Harvard CTSA (The Catalyst), the recent establishment of the Obesity Prevention Center at Boston Children's Hospital, the existence of numerous institutional training grants, outstanding access to patients and clinical materials, and an exciting intellectual environment with clinical and basic investigators working in related areas.